Indole-type derivatives as inhibitors of p38 kinase

Details Indole-type derivatives as inhibitors of p38 kinase Indole-type derivatives as inhibitors of p38 kinase

2005-03-15

2005-03-15

Chang, Celia (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S183000, C514S232800, C514S235200, C514S235800, C540S481000, C544S121000, C544S142000, C544S363000, C544S396000

Reexamination Certificate

active

06867209

ABSTRACT:
The invention is directed to methods to inhibit p38-α kinase using compounds of the formulaand the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, whereinimg id="CUSTOM-CHARACTER-00001" he="3.56mm" wi="5.67mm" file="US06867209-20050315-P00001.TIF" alt="custom character" img-content="character" img-format="tif" ?represents a single or double bond;one Z2is CA or CR8A and the other is CR1, CR12, NR6or N wherein each R1, R6and R8is independently hydrogen or noninterfering substituent;A is —Wi—COXjY wherein Y is COR2or an isostere thereof and R2is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1;as Z3is NR7or O;each R3is independently a noninterfering substituent;n is 0-3;each of L1and L2is a linker;each R4is independently a noninterfering substituent;m is 0-4;Z1is CR5or N wherein R5is hydrogen or a noninterfering substituent;each of 1 and k is an integer from 0-2 wherein the sum of 1 and k is 0-3;Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; andthe distance between the atom of Ar linked to L2and the center of the α ring is 4.5-24 Å.

REFERENCES:
patent: 3316260 (1967-04-01), Shen et al.
patent: 4088765 (1978-05-01), Winn et al.
patent: 4243806 (1981-01-01), Raeymaekers et al.
patent: 4454130 (1984-06-01), Tominaga et al.
patent: 4886809 (1989-12-01), Tamada et al.
patent: 5462934 (1995-10-01), Goto et al.
patent: 5696122 (1997-12-01), Gaster et al.
patent: 5698553 (1997-12-01), Prucher et al.
patent: 5714498 (1998-02-01), Kulagowski et al.
patent: 5726177 (1998-03-01), Halazy et al.
patent: 6410540 (2002-06-01), Goehring et al.
patent: 0 318 235 (1989-05-01), None
patent: 0 431 945 (1991-06-01), None
patent: 0 709 384 (1996-05-01), None
patent: 0 831 090 (1998-03-01), None
patent: 2-184673 (1990-07-01), None
patent: 61-291566 (1996-12-01), None
patent: 9-124631 (1997-09-01), None
patent: WO 9640143 (1996-12-01), None
patent: WO 9726252 (1997-07-01), None
patent: WO 9806715 (1998-02-01), None
patent: WO 9807425 (1998-02-01), None
patent: WO 9828292 (1998-07-01), None
patent: WO 9900357 (1999-01-01), None
patent: WO 9961426 (1999-12-01), None
patent: WO 0012074 (2000-03-01), None
patent: WO 0059904 (2000-03-01), None
patent: WO 0242292 (2002-05-01), None
patent: WO 0244168 (2002-06-01), None
patent: WO 02070491 (2002-09-01), None
Muro et al. “Dihydrobenzofuran derivatives” CA 88:169949 (1978).*
Patani et al. “Bioisosterism: a rational approach in drug design” Chem. Rev. v.96, p. 3147-3176 (1996).*
Schneider et al. “Hyperlipedemia and the . . . ” CA 127:79417 (1996).*
CRC handbook of chemistry and physics 83rd edition (2002).*
De Clerck et al. (1981).Throm. Res23:1-12.
Dukic eet al. (1997).Arch Pharm330:25-28.
Eyers, P.A. et al. “Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution”,Chem and Biol(1995) 5:321-328.
Fischer, “Physical chemical properties and local anesthetic results of an ether substitute of procaine” CA 67:10051 (1996).
Gassman, P. G., “A General Method for the Synthesis of Indoles,” J. Am. Chem. Soc., (1974) 96(17): 5495-5508.
International Search Report dated Jul. 29, 1999.
Jiang, Y. et al., “Characterization of the structure and function of a new mitogen-activated protein kinase (p38β)”J Biol Chem(1996) 271:17920-17926.
Kumar, S. et al. “Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles”,Biochem Biophys Res Comm(1997) 235:533-538.
Li, Z. et al. “The primary structure of p38γ: a new member of p38 group of MAP kinases”,Biochem Biophys Res Comm(1996) 228:334-340.
Murai, Y., et al., “Synthesis of 4-, 5-, 6- and 7-Substituted N-Tosylindoles from Substituted Anilines,”Heterocycles,(1992) 34(5):1017-1029.
Nakai et al. (1994).CA121:222012.
Nakai et al. (1994).CA121:221997.
Oelschlaeger et al. (1988).CA109:73387.
Otsuka Pharm. (1983).CA100:51465.
Otsuka Pharm. (1983).CA100:34414.
Otsuka Pharm. (1984).CA100:68187.
Stein, B. et al. “p38-2, a novel mitogen-activated protein kinase with distinct properties”,J Biol Chem(1997) 272:19509-19517.
Von Strandtmann. (1971).CA80:82713.
Wang, X.S., et al., “Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase”,J Biol Chem(1997) 272:23668-23674.
Wang, Y. et al. “Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family”,J Biol Chem(1998) 273:2161-2168.

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